Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation.

AMPK promotes catabolic and suppresses anabolic cell metabolism to promote cell survival during energetic stress, in part by inhibiting MTORC1, an anabolic kinase requiring sufficient levels of amino acids. We found that cells lacking AMPK displayed increased apoptotic cell death during nutrient stress caused by prolonged amino acid deprivation. We presumed that impaired macroautophagy/autophagy explained this phenotype, as a prevailing view posits that AMPK initiates autophagy (often a pro-survival response) through phosphorylation of ULK1.

Unexpected roles for AMPK in the suppression of autophagy and the reactivation of mTORC1 signaling during prolonged amino acid deprivation.

AMPK promotes catabolic and suppresses anabolic cell metabolism to promote cell survival during energetic stress, in part by inhibiting mTORC1, an anabolic kinase requiring sufficient levels of amino acids. We found that cells lacking AMPK displayed increased apoptotic cell death during nutrient stress caused by prolonged amino acid deprivation. We presumed that impaired autophagy explained this phenotype, as a prevailing view posits that AMPK initiates autophagy (often a pro-survival response) through phosphorylation of ULK1.

Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial.

Background: The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently).

Methods: Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe.

Alkaline intracellular pH (pHi) increases PI3K activity to promote mTORC1 and mTORC2 signaling and function during growth factor limitation.

The conserved protein kinase mTOR (mechanistic target of rapamycin) responds to diverse environmental cues to control cell metabolism and promote cell growth, proliferation, and survival as part of two multiprotein complexes, mTOR complex 1 (mTORC1) and mTORC2. Our prior work demonstrated that an alkaline intracellular pH (pHi) increases mTORC2 activity and cell survival in complete media in part by activating AMP-activated protein kinase, a kinase best known to sense energetic stress. It is important to note that an alkaline pHi represents an underappreciated hallmark of cancer cells that promotes their oncogenic behaviors.

The impact of the COVID-19 pandemic on elective laparoscopic cholecystectomy: A retrospective Cohort study.

The coronavirus disease 2019 (COVID-19) pandemic had a significant impact on elective surgery for benign disease. We examined the effects of COVID-19 related delays on the outcomes of patients undergoing elective laparoscopic cholecystectomy (LC) in an upper gastrointestinal surgery unit in the UK. We have analysed data retrospectively of patients undergoing elective LC between 01/03/2019 to 01/05/2019 and 01/04/2021 to 11/06/2021.

A Retrospective Study on the Impact of COVID-19 on Emergency General Surgery.

Background The coronavirus pandemic has caused global disruption to all aspects of life. This disturbance has been most notable in the medical world. Political, societal, medical, and behavioral alterations have forced emergency surgical practices to adapt.

Use of item response theory to develop a return to work measure for acquired brain injury: The employment feasibility checklist.

Background: The 2001 Feasibility Evaluation Checklist (FEC) is an assessment of work readiness for individuals with acquired brain injury (ABI). It establishes the integrity of basic safety, productivity, and interpersonal factors in neurorehabilitation and vocational settings. This study represents an effort to further develop the FEC to increase its clinical utility.

Marine iodine emissions in a changing world.

Iodine is a critical trace element involved in many diverse and important processes in the Earth system. The importance of iodine for human health has been known for over a century, with low iodine in the diet being linked to goitre, cretinism and neonatal death. Research over the last few decades has shown that iodine has significant impacts on tropospheric photochemistry, ultimately impacting climate by reducing the radiative forcing of ozone (O) and air quality by reducing extreme O concentrations in polluted regions.

Bariatric Surgery as a Viable Treatment for Idiopathic Intracranial Hypertension: a Case Series and Review of Literature.

Purpose: Idiopathic intracranial hypertension is a significant cause of preventable blindness. Patients suffer from debilitating headaches, pulsatile tinnitus, nausea, vomiting, photophobia and radicular pain. At this rate, treatment cost will increase to 462.

The impact of bariatric surgery on the resolution of obstructive sleep apnoea.

Objective: Obesity is associated with a high incidence of obstructive sleep apnoea (OSA). Bariatric surgery is postulated to lead to OSA resolution, but there is inconclusive evidence on its efficacy. We used objective measurements to determine the rate of resolution or improvement of OSA in patients who had bariatric procedures in our unit.

Arctic pathways of Pacific Water: Arctic Ocean Model Intercomparison experiments.

Pacific Water (PW) enters the Arctic Ocean through Bering Strait and brings in heat, fresh water, and nutrients from the northern Bering Sea. The circulation of PW in the central Arctic Ocean is only partially understood due to the lack of observations. In this paper, pathways of PW are investigated using simulations with six state-of-the art regional and global Ocean General Circulation Models (OGCMs).

Symptomatic diaphragmatic herniation following open and minimally invasive oesophagectomy: experience from a UK specialist unit.

Background: The uptake of minimally invasive oesophagectomy (MIO) in the UK has increased dramatically in recent years. Post-oesophagectomy diaphragmatic hernias (PODHs) are rare, but may be influenced by the type of approach to resection. The aim of this study was to compare the incidence of symptomatic PODH following open and MIO in a UK specialist centre.

Ocean processes at the Antarctic continental slope.

The Antarctic continental shelves and slopes occupy relatively small areas, but, nevertheless, are important for global climate, biogeochemical cycling and ecosystem functioning. Processes of water mass transformation through sea ice formation/melting and ocean-atmosphere interaction are key to the formation of deep and bottom waters as well as determining the heat flux beneath ice shelves. Climate models, however, struggle to capture these physical processes and are unable to reproduce water mass properties of the region.

Outcome of gastro-oesophageal reflux-related respiratory manifestations after laparoscopic fundoplication.

Aims: Patients with refractory respiratory symptoms related to gastro-oesophageal reflux disease (GORD) such as asthma and cough are being referred for laparoscopic fundoplication (LFP), as recommended by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). However there are limited data regarding symptomatic response to fundoplication in this group of patients.

Method: A 7 year retrospective review was performed to study the efficacy of LFP in the treatment of patients with respiratory manifestations of GORD.

Has integrated 18F FDG PET/CT improved staging, reduced early recurrence or increased survival in oesophageal cancer?

Background: Survival in oesophageal cancer remains poor with high post-operative recurrence rates. PET/CT was introduced to the Three-Counties Cancer Network (3CCN) in 2006 to detect 'occult' metastatic disease not seen with conventional staging modalities. This study aims to determine whether the introduction of Integrated fluorodeoxyglucose (18F) Positron Emission Tomography (PET/CT) has changed the management, improved survival or reduced the rate of early post-operative recurrence in patients with operable oesophageal cancer.

Endoscopic Raman spectroscopy enables objective diagnosis of dysplasia in Barrett's esophagus.

Background: Early detection and targeted endoscopic resection of Barrett's esophagus-associated high-grade dysplasia (HGD) can prevent progression to invasive esophageal malignancy. Raman spectroscopy, a highly sophisticated analytical technique, has been translated into an endoscopic tool to facilitate rapid, objective diagnosis of dysplasia in the esophagus.

Objective: To evaluate the ability of endoscopic Raman spectroscopy (ERS) to objectively detect esophageal HGD and adenocarcinoma.

Gastric schwannoma: a benign tumour often mistaken clinically, radiologically and histopathologically for a gastrointestinal stromal tumour--a case series.

Introduction: Gastric schwannomas are rare mesenchymal tumours that arise from the nerve plexus of the gut wall. They present with non-specific symptoms and are often detected incidentally. Pre-operative investigation is not pathognomonic and many are therefore diagnosed as gastrointestinal stromal tumours (GISTs).

A 5-year prospective review of posterior partial fundoplication in the management of gastroesophageal reflux disease.

Introduction: Laparoscopic Nissen fundoplication is the most common surgical procedure performed for gastroesophageal reflux disease (GORD). It is however associated with a number of mechanical complications with as many as one in three patients experiencing troublesome dysphagia or gas bloat. Partial fundoplication, either posterior or anterior, has been advocated in an attempt to reduce these problems.

Ice-age survival of Atlantic cod: agreement between palaeoecology models and genetics.

Scant scientific attention has been given to the abundance and distribution of marine biota in the face of the lower sea level, and steeper latitudinal gradient in climate, during the ice-age conditions that have dominated the past million years. Here we examine the glacial persistence of Atlantic cod (Gadus morhua) populations using two ecological-niche-models (ENM) and the first broad synthesis of multi-locus gene sequence data for this species. One ENM uses a maximum entropy approach (Maxent ); the other is a new ENM for Atlantic cod, using ecophysiological parameters based on observed reproductive events rather than adult distribution.

The diagnosis of invasive lobular breast carcinoma. Does MRI have a role?

Invasive lobular breast carcinoma accounts for approximately 15% of all breast cancers and is difficult to detect using conventional breast imaging techniques. We report a comparison between clinical, ultrasound scan (USS), mammographic and magnetic resonance imaging (MRI) of 22 patients with invasive lobular breast carcinomas. Actual tumour size was ascertained by histopathology.

Co-expression of vascular endothelial growth factor C (VEGF-C) and c-erbB2 in human breast carcinoma.

Vascular endothelial growth factor C (VEGF-C) has angiogenic and lymphangiogenic properties and is associated with the development of lymphatic metastases in a number of epithelial malignancies. The aim of this study was to determine VEGF-C protein expression in a series of breast carcinomas and correlate this with axillary lymph node (LN) metastases, the presence of lympho-vascular invasion (LVI), bone marrow micro-metastases (BMM) and other clinico-pathological data including oestrogen receptor (ER) and c-erbB2 status. VEGF-C expression was determined by immunohistochemistry (IHC) in 51 tumours.

Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer. Union Internacional Contra la Cancrum/American Joint Committee on Cancer.

Background: In the surgical management of gastric carcinoma, regional lymphatic spread is of prognostic importance. The fifth edition of the Union Internacional Contra la Cancrum classification has been shown to be reproducible, practical and of significant prognostic use. The tumour node metastasis (TNM) system requires at least 15 lymph nodes to be acquired and examined for staging to be accurate.

Plasma levels of vascular endothelial growth factor (VEGF) and its receptor, Flt-1, in haematological cancers: a comparison with breast cancer.

Raised plasma VEGF is found in some cancers but levels of its receptor soluble Flt-1 (sFlt-1) are unreported. Hypothesising increased levels to be present in haematological cancers, we measured both by ELISA in 22 patients with haematological cancer, 22 with breast cancer, and in age- and sex-matched controls. VEGF was raised in both patients groups compared to controls (P < 0.

Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor.

Abnormal platelet activation and an increased risk of thrombosis are frequent findings in cancer. As soluble adhesion molecule P-selectin is being increasingly recognized as reflecting increased platelet activation, we hypothesized raised levels in patients with cancer, obtaining plasma from 24 patients with a cross-section of haematological cancers, 41 with breast cancer, and from an equal number of healthy controls for each patient group. Levels of soluble P-selectin were compared with those of von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) activity and fibrinogen (markers of endothelial integrity, fibrinolysis and coagulation, respectively).

Soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) in inflammatory vascular disease, atherosclerotic vascular disease, and in cancer.

Cell surface adhesion molecule expression is likely to be important in inflammation, atherosclerosis and cancer, and soluble forms of many of these molecules are present in plasma. We measured levels of the soluble form of platelet endothelial cell adhesion molecule-1 (sPECAM) by ELISA in the serum of 77 patients with frank atherosclerosis, 69 patients with inflammatory connective tissue disease, and 39 patients with cancer. Each group of patients was controlled by an equal number of age- and sex-matched healthy subjects.